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Blood‐cell‐based biomarker detection of Alzheimer’s disease
Author(s) -
Cliff Richard O
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.046027
Subject(s) - asymptomatic , biomarker , whole blood , oligomer , medicine , blood test , disease , immunology , pathology , chemistry , biochemistry , organic chemistry
Background There is an urgent need for early screening diagnostics for Alzheimer’s disease (AD), cases continue to increase without effective diagnosis and treatment solutions. There is no test to diagnose AD at its earliest stages in healthy asymptomatic individuals to determine disease status. Fluid biomarkers, particularly blood‐based, could have the capacity to be widely implemented as diagnostic screens and to rule‐in/rule‐out further invasive and expensive testing. Amyloid‐beta (Aβ) oligomers continue to be a compelling target for therapeutics and diagnostics, are present in blood and are bound by blood cells. Given the accumulated evidence that Aβ oligomers are present in blood; we are developing a novel early detection blood cell‐based biomarker test using proprietary peptide ligands before any signs of AD in healthy asymptomatic individuals, much like a cholesterol blood test for cardiovascular disease. Method Our technology, Pronucleon™ peptides, involves custom‐synthesized peptides that mimic the misfolding region of proteins such as Aβ. We’ve established specific, sensitive and selective detection of Aβ oligomers with our peptides using spectroscopic techniques. For this study we measured the binding capacity index (BCI) of blood cells using the following assay: diluted whole blood was incubated with or without our proprietary stabilized Aβ oligomer; fluorescently‐labeled Pronucleon™ peptide was then incubated with the blood samples followed by flow cytometric analysis. We compared the fluorescence intensity of each sample, one with and one without the stabilized Aβ oligomer. The assay was performed on 60 clinical samples (n=20 for each Control, MCI and AD) followed by statistical analysis to confirm any differences within and between the patient groups. Result Pronucleon™ peptides displayed specificity and sensitivity for Aβ oligomers; peptides also showed increased binding to AD blood cells as compared to normal; our cell‐based flow cytometry assay exhibited differentiation in BCI scoring between healthy and AD samples. Conclusion These results set the stage for further development of an exciting innovative approach toward a screening tool for diagnosing Alzheimer’s disease, allowing the primary care setting in the medical community, the AD therapeutic community and the public an opportunity to address early detection of this disease before its symptoms appear.